Abstract

Autografting (AutoSCT) has been limited by high-relapse rates and conventional allografting (AlloSCT) by excessive TRM and toxicity in the treatment of Multiple Myeloma (MM). Reduced intensity conditioning for transplant (RICT), a less toxic procedure for AlloSCT that aims to exploit graft versus tumor effect, has been shown to achieve remissions in MM. High-dose therapy/AutoSCT followed shortly thereafter by RICT might improve outcomes in MM as compared to AutoSCT or conventional AlloSCT used alone. We compared two retrospective cohort of patients who underwent either tandem AutoSCT (HDT consisted of Melphalan 200 mg/m2) or AutoSCT followed closely by related RICT (patients with HLA-matched siblings). The two groups were matched for pre-transplant therapy, disease status at transplant, time from diagnosis to transplant. GVHD prophylaxis for RICT patients consisted of CyA/MTX. The major results are summarized in the Table. In the AutoSCT/RICT group the complete remission rate was higher (p=0.004) and the risk of disease progression after transplant was significantly reduced (p=0.005). All patients who reached CR responded after full chimerism and GVHD developed. This finding confirms the existence of a graft-versus-myeloma effect. Since the first clinical signs of response in remitters patients were noted between 70 and 120 days and maximum response between 160 and 200 days after RICT (after DLI in one patient), these responses should be considered immunological responses. These data suggest than an allograft following an AutoSCT significantly reduces the incidence of disease progression.

Tandem ASCT (N=35)ASCT + RICT (n=20)
Age, median 56 (range, 38–66) 51 (range, 34–63)  
Median prior cycles of Chemoth. 4 (range, 3–6) 4 (range, 3–6)  
Time from Dx to 1st AutoSCT (median mo.) 6 (range, 5–60) 9 (range, 7–42)  
Conditioning Regimen for AutoSCT Melphalan (200 mg/m2) Melphalan (200 mg/m2)  
Conditioning Regimen for RICT --- TBI/Fludarabine  
Complete Remission 14% 50% p=0.004) 
Disease-Free Survival at 3 yrs 11% 45% (p=0.005) 
Overall Survival at 3 yrs 66% 70% (p=NS) 
Median Follow-Up (mo.) 30 (range, 6–104) 38 (range, 5–59)  
Transplant-Related Mortality 0% 0%  
Median days from AutoSCT to RICT --- 80  
Tandem ASCT (N=35)ASCT + RICT (n=20)
Age, median 56 (range, 38–66) 51 (range, 34–63)  
Median prior cycles of Chemoth. 4 (range, 3–6) 4 (range, 3–6)  
Time from Dx to 1st AutoSCT (median mo.) 6 (range, 5–60) 9 (range, 7–42)  
Conditioning Regimen for AutoSCT Melphalan (200 mg/m2) Melphalan (200 mg/m2)  
Conditioning Regimen for RICT --- TBI/Fludarabine  
Complete Remission 14% 50% p=0.004) 
Disease-Free Survival at 3 yrs 11% 45% (p=0.005) 
Overall Survival at 3 yrs 66% 70% (p=NS) 
Median Follow-Up (mo.) 30 (range, 6–104) 38 (range, 5–59)  
Transplant-Related Mortality 0% 0%  
Median days from AutoSCT to RICT --- 80  

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